WO2001083490A1 - Derive de pyrazole substitue - Google Patents

Derive de pyrazole substitue Download PDF

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Publication number
WO2001083490A1
WO2001083490A1 PCT/EP2001/004418 EP0104418W WO0183490A1 WO 2001083490 A1 WO2001083490 A1 WO 2001083490A1 EP 0104418 W EP0104418 W EP 0104418W WO 0183490 A1 WO0183490 A1 WO 0183490A1
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WO
WIPO (PCT)
Prior art keywords
compound
formula
combination
medicaments
reaction
Prior art date
Application number
PCT/EP2001/004418
Other languages
German (de)
English (en)
Inventor
Alexander Straub
Cristina Alonso-Alija
Armin Kern
Johannes-Peter Stasch
Klaus Dembowsky
Original Assignee
Bayer Aktiengesellschaft
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer Aktiengesellschaft filed Critical Bayer Aktiengesellschaft
Priority to AU2001256305A priority Critical patent/AU2001256305A1/en
Publication of WO2001083490A1 publication Critical patent/WO2001083490A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a substituted pyrazole derivative, a process for its preparation and its use as a medicament, in particular as a medicament for the treatment of cardiovascular diseases.
  • WO 98/16223 discloses the use of l-benzyl-3- (substituted-hetaryl) -condensed pyrazole derivatives for the treatment of special diseases of the cardiovascular system and the central nervous system.
  • WO 98/16507 discloses heterocyclylmethyl-substituted pyrazole derivatives and their
  • WO 98/23619 also discloses substituted pyrazole derivatives for the treatment of cardiovascular diseases.
  • the present invention relates to a substituted pyrazole derivative of the formula (I)
  • the compound of the formula (I) according to the invention can also be present in the form of hydrate or in the form of its salts.
  • salts with organic or inorganic bases or acids may be mentioned here.
  • Physiologically acceptable salts are preferred in the context of the present invention.
  • Physiologically acceptable salts of the compound according to the invention can be salts of the substance according to the invention with mineral acids, carboxylic acids or sulfonic acids.
  • mineral acids for example, particular preference is given to Salts with hydrochloric acid,
  • Hydrobromic acid sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, naphthalenedisulfonic acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid, fumaric acid, maleic acid or benzoic acid.
  • Physiologically acceptable salts can also be metal or ammonium salts of the compound according to the invention.
  • metal or ammonium salts of the compound according to the invention.
  • Sodium, potassium, magnesium or calcium salts and also ammonium salts derived from ammonia, or organic amines such as ethylamine, di- or triethylamine, di- or triethanolamine, dicyclohexylamine, dimethylaminoethanol,
  • the compound according to the invention can exist in stereoisomeric forms (enantiomers).
  • the invention relates to both the enantiomers and their mixture.
  • the racemic forms can be uniformly stereoisomerically known
  • the compound of formula (I) according to the invention shows an unforeseeable, valuable pharmacological spectrum of action. In particular, it leads to vascular relaxation, inhibition of platelet aggregation and a reduction in blood pressure, as well as an increase in coronary blood flow. These effects are mediated by direct stimulation of soluble guanylate cyclase and an intracellular increase in cGMP.
  • the compound of the formula (I) according to the invention enhances the action of substances which inhibit the cGMP
  • cardiovascular diseases such as for the treatment of high blood pressure and heart failure, stable and unstable angina pectoris, peripheral and cardiac vascular diseases, of arrhythmias, for the treatment of thromboembolic diseases and ischemia such as myocardial infarction, stroke, transitory and ischemic attacks , peripheral circulatory disorders, prevention of restenosis such as after thrombolysis therapies, percutaneous transluminal angioplasty (PTA), percutaneous transluminal
  • Coronary angioplasties bypass and for the treatment of arteriosclerosis, asthmatic diseases and diseases of the genitourinary system such as prostate hypertrophy, erectile dysfunction, female sexual dysfunction and incontinence.
  • the compound of formula (I) described in the present invention also represents an active ingredient for combating diseases in the central nervous system which are characterized by disorders of the NO / cGMP system.
  • diseases of the central nervous system such as anxiety, tension and depression, central nervous system-related sexual dysfunctions and sleep disorders, as well as for the regulation of pathological disorders in the intake of food, beverages and addictive substances.
  • the active ingredient is also suitable for regulating cerebral blood flow and is therefore an effective means of combating migraines.
  • the compound of formula (I) according to the invention can be used to combat painful conditions.
  • the invention comprises the combination of the compound of the formula (I) according to the invention with organic nitrates and NO donors.
  • Organic nitrates and NO donors in the context of the invention are generally substances which develop their therapeutic effect through the release of NO or NO species.
  • Sodium nitroprusside, nitroglycerin, isosorbide di-nitrate, isosorbide mononitrate, molsidomine and SIN-1 are preferred.
  • the invention also includes combination with compounds that inhibit the degradation of cyclic guanosine monophosphate (cGMP).
  • cGMP cyclic guanosine monophosphate
  • These are in particular inhibitors of phosphodiesterases 1, 2 and 5; Nomenclature according to Beavo and Reif-Snyder (1990) TiPS 11 pp. 150 to 155. These inhibitors potentiate the action of the compound according to the invention and increase the desired pharmacological effect.
  • the compound of the formula (II) is obtainable in a multistage synthesis from the sodium salt of the cyanobenzofruvic acid ethyl ester (Borsche and Manteuffel, Liebigs. Ann. Chem. 1934, 512, 97) known from the literature.
  • This ethyl pyridine derivative l- (2-fluorobenzyl) -IH-pyrazolo [3,4-b] pyridine-3-carboxylate is subjected to a multistage sequence consisting of converting the ester with ammonia into the corresponding amide, dehydration with a dehydrating agents such as trifluoroacetic anhydride to give the corresponding nitrile derivative, reaction of the nitrile derivative with sodium methylate and final reaction with ammonium chloride are converted into the compound of the formula (II).
  • inorganic or organic bases can be used as bases.
  • bases preferably include alkali metal hydroxides such as sodium hydroxide or potassium hydroxide, alkaline earth metal hydroxides such as barium hydroxide, alkali metal carbonates such as sodium carbonate or potassium carbonate, alkaline earth metal carbonates such as calcium carbonate, or alkali or alkaline earth metal alcohol such as
  • Inert organic solvents are suitable as solvents. These include ethers such as diethyl ether or tetrahydrofuran, DME, dioxane, alcohols such as methanol and ethanol, halogenated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane, 1,2-dichloroethane, trichloroethane, tetrachloroethane, 1,2-dichloroethane or
  • Trichlorethylene hydrocarbons such as benzene, xylene, toluene, hexane, cyclohexane, or petroleum fractions, nitromethane, dimethylformamide, acetone, acetonitrile or hexamethylphosphoric triamide. It is also possible to use mixtures of the solvents. Tetrahydrofuran, dimethylformamide, toluene, dioxane or dimethoxyethane is particularly preferred.
  • the reaction is carried out with heating to temperatures between 60 ° C and 110 ° C and normal pressure.
  • the reaction mixture is allowed to react for about 5-24 hours, preferably 12 to 24 hours.
  • the compound of the formula (III) is then obtained by cleaving the azo group.
  • metals in particular zinc, can be used as reducing agents in the presence of mineral acids such as hydrochloric acid, Na 2 SO 4 , boranes or hydrogen in the presence of a catalyst.
  • the use of hydrogen in the presence of Raney-Ni is preferred.
  • the solvents mentioned above can be used as solvents.
  • Dimethylformamide (DMF) is particularly preferred.
  • the reaction is preferably carried out with heating, for example at 50-80 ° C., and a hydrogen pressure of 30 to 80 bar, preferably 50 to 70 bar. The reactants are allowed to react for about 24 hours.
  • the compound of formula (III) is reacted with a hydroxyl-protected 2-hydroxyacetaldehyde and the imino group formed is then reduced.
  • the conventional, the skilled person come as protective groups for the hydroxy function known hydroxyl protecting groups in question.
  • the solvents mentioned above can be used as solvents. Methanol is particularly preferred.
  • the reaction is preferably carried out at room temperature and normal pressure.
  • the imino group obtained by this reaction is preferably reduced in situ to the corresponding secondary amino group.
  • the reducing agents known to the person skilled in the art for this reaction such as alkali metal hydrides, for example
  • Lithium aluminum hydride or sodium borohydride or sodium cyanoborohydride, alkali metals such as sodium in ethanol or hydrogen can be used in the presence of a catalyst. Reduction with sodium cyanoborohydride in the presence of a dehydrating agent such as molecular sieve is preferred according to the invention. The reduction is preferably carried out at room temperature and is complete after about 2 to 8 hours, preferably after about 3 to 5 hours.
  • the compound of formula (I) according to the invention is obtained from the hydroxyl-protected ethanolamine derivative thus obtained by deprotection of the hydroxyl group and subsequent reaction with glyoxal.
  • deprotectant depends on the selected protective group.
  • fluoride compounds such as tetrabutylammonium fluoride can preferably be used under conditions which are conventional for these reactions and known to the person skilled in the art.
  • the reaction with glyoxal preferably in the form of its hydrate, is carried out under a protective gas atmosphere, for example under nitrogen or a noble gas such as argon.
  • the reaction is carried out at room temperature for about 12 to 24 hours.
  • the solvents mentioned above can also be used as solvents for these last steps, tetrahydrofuran (THF) being particularly preferred.
  • THF tetrahydrofuran
  • acetal compounds thereof can also be used, if appropriate in the presence of acids.
  • BABA n-butyl acetate / n-butanol / glacial acetic acid / phosphate buffer pH 6
  • the solution obtained from 1. is mixed with 61.25 ml (60.77 g, 0.613 mol) of dimethylammoacrolein and 56.28 ml (83.88 g, 0.736 mol) of trifluoroacetic acid and boiled under argon for 3 days.
  • the solvent is then evaporated in vacuo, the residue is poured into 2 liters of water and extracted three times with 1 liter of ethyl acetate.
  • the free base is obtained by shaking out with dilute NaHCO 3 solution and extracting with ethyl acetate.
  • the solid which is insoluble in both phases is filtered off with suction.
  • the ethyl acetate phase also contains small amounts of the free base.
  • Rabbits are anesthetized and bled by the blow of the neck.
  • the aorta is removed, adherent tissue is removed, divided into 1.5 mm wide rings and individually pretensioned in 5 ml organ baths with carbohydrate gas at 37 ° C
  • Phenylephrine added cumulatively to the bath in increasing concentration. After several control cycles, the substance to be examined is examined in increasing doses in each further run and the level of the contraction is compared with the level of the contraction achieved in the last previous run. From this, the concentration is calculated which is required to reduce the level of the control value by 50% (ICso).
  • Compound (I): IC 50 1200 nM
  • mice Male Wistar rats with a body weight of 300-350 g are anesthetized with thiopental (100 mg / kg ip). After tracheotomy, a catheter for measuring blood pressure is inserted into the femoral artery and a catheter for substance administration into the femoral vein. The substance to be tested is administered intravenously in Transcutol / Cremophor / EL / H 2 O (10% / 10% / 80%) in a volume of 1 ml / kg. Compound (I) induces a dose-dependent and long-lasting lowering of blood pressure in rats. After intravenous administration of 0.1 mg / kg and 0.3 mg / kg, a maximum drop in blood pressure of -17 mm and - 41 mm Hg was observed.

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Cardiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un dérivé de pyrazole substitué correspondant à la formule (I), un procédé permettant de produire ce dérivé, et son utilisation comme médicament, en particulier comme médicament pour le traitement de maladies cardio-vasculaires.
PCT/EP2001/004418 2000-04-28 2001-04-19 Derive de pyrazole substitue WO2001083490A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001256305A AU2001256305A1 (en) 2000-04-28 2001-04-19 Substituted pyrazole derivative

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10021069A DE10021069A1 (de) 2000-04-28 2000-04-28 Substituiertes Pyrazolderivat
DE10021069.4 2000-04-28

Publications (1)

Publication Number Publication Date
WO2001083490A1 true WO2001083490A1 (fr) 2001-11-08

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AU (1) AU2001256305A1 (fr)
DE (1) DE10021069A1 (fr)
WO (1) WO2001083490A1 (fr)

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003000642A3 (fr) * 2001-06-21 2003-03-27 Nicox Sa Medicaments contre les douleurs chroniques
WO2003101456A1 (fr) * 2002-06-03 2003-12-11 Bayer Healthcare Ag Utilisation de composes stimulant le gmp cyclique
EP1522314A1 (fr) * 2002-06-26 2005-04-13 Ono Pharmaceutical Co., Ltd. Remedes pour les maladies provoquees par la contraction ou la dilatation vasculaire
DE102007026392A1 (de) 2007-06-06 2008-12-11 Bayer Healthcare Ag Lösungen für die Perfusion und Konservierung von Organen und Geweben
WO2012028647A1 (fr) 2010-09-03 2012-03-08 Bayer Pharma Aktiengesellschaft Azahétérocycles bicycliques et leur utilisation
WO2012165399A1 (fr) 2011-05-30 2012-12-06 アステラス製薬株式会社 Composé imidazopyridine
WO2013131923A1 (fr) 2012-03-06 2013-09-12 Bayer Intellectual Property Gmbh Azabicyles substitués et leur utilisation
US8741910B2 (en) 2008-11-25 2014-06-03 Merck Sharp & Dohme Corp. Soluble guanylate cyclase activators
WO2014084312A1 (fr) 2012-11-30 2014-06-05 アステラス製薬株式会社 Composé imidazopyridine
US8765769B2 (en) 2010-07-09 2014-07-01 Bayer Intellectual Property Gmbh Ring-fused 4-aminopyrimidines and use thereof as stimulators of soluable guanylate cyclases
JP2014523895A (ja) * 2011-07-06 2014-09-18 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング ヘテロアリール置換ピラゾロピリジン類およびその使用
US8859569B2 (en) 2011-09-02 2014-10-14 Bayer Pharma Aktiengesellschaft Substituted annellated pyrimidines and use thereof
US9023849B2 (en) 2012-01-11 2015-05-05 Bayer Intellectual Property Gmbh Substituted fused imidazoles and pyrazoles and use thereof
US9090610B2 (en) 2011-04-21 2015-07-28 Bayer Intellectual Property Gmbh Fluoroalkyl-substituted pyrazolopyridines and use thereof
US9133191B2 (en) 2012-01-11 2015-09-15 Bayer Intellectual Property Gmbh Substituted triazine derivatives and use thereof as stimulators of soluble guanylate cyclase
US9216978B2 (en) 2010-07-09 2015-12-22 Bayer Intellectual Property Gmbh Ring-fused pyrimidines and triazines and use thereof for the treatment and/or prophylaxis of cardiovascular diseases
US9266871B2 (en) 2013-03-01 2016-02-23 Bayer Pharma Aktiengesellschaft Trifluoromethyl-substituted fused pyrimidines and their use
US9284301B2 (en) 2010-03-25 2016-03-15 Merck Sharp & Dohme Corp. Soluble guanylate cyclase activators
US9365574B2 (en) 2010-05-27 2016-06-14 Merck Sharp & Dohme Corp. Soluble guanylate cyclase activators
US9505786B2 (en) 2012-01-11 2016-11-29 Bayer Pharma Aktiengesellschaft Substituted annulated triazines and use thereof
US9605008B2 (en) 2013-07-10 2017-03-28 Bayer Pharma Aktiengesellschaft Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
WO2017106175A2 (fr) 2015-12-14 2017-06-22 Ironwood Pharmaceuticals, Inc. Utilisation de stimulateurs de la sgc pour le traitement d'un dysfonctionnement du sphincter gastro-intestinal
WO2018111795A2 (fr) 2016-12-13 2018-06-21 Ironwood Pharmaceuticals, Inc. Utilisation de stimulateurs de sgc pour le traitement de la motilité œsophagienne
WO2020014504A1 (fr) 2018-07-11 2020-01-16 Cyclerion Therapeutics, Inc. Utilisation de stimulateurs gcs pour le traitement de maladies mitochondriales
WO2021167458A1 (fr) 2020-02-21 2021-08-26 Universiteit Maastricht Utilisation d'un stimulateur de guanylate cyclase soluble (sgc) ou d'une combinaison d'un stimulateur de sgc et d'un activateur de sgc dans des conditions dans lesquelles le groupe hème de sgc est oxydé ou sgc est déficient en hème
US11242335B2 (en) 2017-04-11 2022-02-08 Sunshine Lake Pharma Co., Ltd. Fluorine-substituted indazole compounds and uses thereof

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR031176A1 (es) * 2000-11-22 2003-09-10 Bayer Ag Nuevos derivados de pirazolpiridina sustituidos con piridina
DE10132416A1 (de) * 2001-07-04 2003-01-16 Bayer Ag Neue Morpholin-überbrückte Pyrazolopyridinderivate

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998016223A1 (fr) * 1996-10-14 1998-04-23 Bayer Aktiengesellschaft Utilisation de 1-benzal-3-derives condenses (hetaryl-substitues) de pyrazol pour le traitement de certaines affections du systeme cardiovasculaire et du systeme nerveux central
WO1998023619A1 (fr) * 1996-11-26 1998-06-04 Bayer Aktiengesellschaft Nouveaux derives de pyrazole substitues pour le traitement de maladies cardio-vasculaires
DE19834045A1 (de) * 1998-07-29 2000-02-03 Bayer Ag (4-Amino-5-ethylpyrimidin-2-yl)-1-(2-fluorbenzyl)-1H-pyrazolo[3,4-b]pyridin
DE19920352A1 (de) * 1999-05-04 2000-11-09 Bayer Ag Substituiertes Pyrazolderivat

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998016223A1 (fr) * 1996-10-14 1998-04-23 Bayer Aktiengesellschaft Utilisation de 1-benzal-3-derives condenses (hetaryl-substitues) de pyrazol pour le traitement de certaines affections du systeme cardiovasculaire et du systeme nerveux central
WO1998023619A1 (fr) * 1996-11-26 1998-06-04 Bayer Aktiengesellschaft Nouveaux derives de pyrazole substitues pour le traitement de maladies cardio-vasculaires
DE19834045A1 (de) * 1998-07-29 2000-02-03 Bayer Ag (4-Amino-5-ethylpyrimidin-2-yl)-1-(2-fluorbenzyl)-1H-pyrazolo[3,4-b]pyridin
DE19920352A1 (de) * 1999-05-04 2000-11-09 Bayer Ag Substituiertes Pyrazolderivat

Cited By (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7696230B2 (en) 2001-06-21 2010-04-13 Nicox S.A. Drugs for chronic pains
WO2003000642A3 (fr) * 2001-06-21 2003-03-27 Nicox Sa Medicaments contre les douleurs chroniques
US7199141B2 (en) 2001-06-21 2007-04-03 Nicox S.A. Drugs for chronic pains
US7812039B2 (en) 2001-06-21 2010-10-12 Nicox S.A. Drugs for chronic pains
WO2003101456A1 (fr) * 2002-06-03 2003-12-11 Bayer Healthcare Ag Utilisation de composes stimulant le gmp cyclique
US8765783B2 (en) 2002-06-26 2014-07-01 Ono Pharmaceuticals Co., Ltd. Pharmaceutical composition for treatment of disease due to vascular constriction or vasodilation
EP1522314A4 (fr) * 2002-06-26 2009-09-16 Ono Pharmaceutical Co Remedes pour les maladies provoquees par la contraction ou la dilatation vasculaire
EP1522314A1 (fr) * 2002-06-26 2005-04-13 Ono Pharmaceutical Co., Ltd. Remedes pour les maladies provoquees par la contraction ou la dilatation vasculaire
DE102007026392A1 (de) 2007-06-06 2008-12-11 Bayer Healthcare Ag Lösungen für die Perfusion und Konservierung von Organen und Geweben
US8741910B2 (en) 2008-11-25 2014-06-03 Merck Sharp & Dohme Corp. Soluble guanylate cyclase activators
US9284301B2 (en) 2010-03-25 2016-03-15 Merck Sharp & Dohme Corp. Soluble guanylate cyclase activators
US9365574B2 (en) 2010-05-27 2016-06-14 Merck Sharp & Dohme Corp. Soluble guanylate cyclase activators
US9216978B2 (en) 2010-07-09 2015-12-22 Bayer Intellectual Property Gmbh Ring-fused pyrimidines and triazines and use thereof for the treatment and/or prophylaxis of cardiovascular diseases
US8765769B2 (en) 2010-07-09 2014-07-01 Bayer Intellectual Property Gmbh Ring-fused 4-aminopyrimidines and use thereof as stimulators of soluable guanylate cyclases
WO2012028647A1 (fr) 2010-09-03 2012-03-08 Bayer Pharma Aktiengesellschaft Azahétérocycles bicycliques et leur utilisation
DE102010040233A1 (de) 2010-09-03 2012-03-08 Bayer Schering Pharma Aktiengesellschaft Bicyclische Aza-Heterocyclen und ihre Verwendung
US9096592B2 (en) 2010-09-03 2015-08-04 Bayer Intellectual Property Gmbh Bicyclic aza heterocycles, and use thereof
US9090610B2 (en) 2011-04-21 2015-07-28 Bayer Intellectual Property Gmbh Fluoroalkyl-substituted pyrazolopyridines and use thereof
WO2012165399A1 (fr) 2011-05-30 2012-12-06 アステラス製薬株式会社 Composé imidazopyridine
JP2014523895A (ja) * 2011-07-06 2014-09-18 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング ヘテロアリール置換ピラゾロピリジン類およびその使用
US8859569B2 (en) 2011-09-02 2014-10-14 Bayer Pharma Aktiengesellschaft Substituted annellated pyrimidines and use thereof
US9505786B2 (en) 2012-01-11 2016-11-29 Bayer Pharma Aktiengesellschaft Substituted annulated triazines and use thereof
US9133191B2 (en) 2012-01-11 2015-09-15 Bayer Intellectual Property Gmbh Substituted triazine derivatives and use thereof as stimulators of soluble guanylate cyclase
US9023849B2 (en) 2012-01-11 2015-05-05 Bayer Intellectual Property Gmbh Substituted fused imidazoles and pyrazoles and use thereof
WO2013131923A1 (fr) 2012-03-06 2013-09-12 Bayer Intellectual Property Gmbh Azabicyles substitués et leur utilisation
US9498480B2 (en) 2012-03-06 2016-11-22 Bayer Intellectual Property Gmbh Substituted azabicycles and use thereof
WO2014084312A1 (fr) 2012-11-30 2014-06-05 アステラス製薬株式会社 Composé imidazopyridine
US9266871B2 (en) 2013-03-01 2016-02-23 Bayer Pharma Aktiengesellschaft Trifluoromethyl-substituted fused pyrimidines and their use
US9605008B2 (en) 2013-07-10 2017-03-28 Bayer Pharma Aktiengesellschaft Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
WO2017106175A2 (fr) 2015-12-14 2017-06-22 Ironwood Pharmaceuticals, Inc. Utilisation de stimulateurs de la sgc pour le traitement d'un dysfonctionnement du sphincter gastro-intestinal
WO2018111795A2 (fr) 2016-12-13 2018-06-21 Ironwood Pharmaceuticals, Inc. Utilisation de stimulateurs de sgc pour le traitement de la motilité œsophagienne
US11242335B2 (en) 2017-04-11 2022-02-08 Sunshine Lake Pharma Co., Ltd. Fluorine-substituted indazole compounds and uses thereof
WO2020014504A1 (fr) 2018-07-11 2020-01-16 Cyclerion Therapeutics, Inc. Utilisation de stimulateurs gcs pour le traitement de maladies mitochondriales
WO2021167458A1 (fr) 2020-02-21 2021-08-26 Universiteit Maastricht Utilisation d'un stimulateur de guanylate cyclase soluble (sgc) ou d'une combinaison d'un stimulateur de sgc et d'un activateur de sgc dans des conditions dans lesquelles le groupe hème de sgc est oxydé ou sgc est déficient en hème

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Publication number Publication date
DE10021069A1 (de) 2001-10-31
AU2001256305A1 (en) 2001-11-12

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